A trial to learn how safe AZD4512 is with and without other cancer drugs and how it works in the bodies of people with B-cell non-Hodgkin lymphoma (B-NHL)

Prior treatment

• 1.Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression. Participants with a prior history of CNS localization of lymphoma who received treatment are eligible provided that there is no evidence of CNS involvement at study entry as documented by CSF analysis and/or brain MRI.
• Previous dosing with AZD4512 in the present study or participants with a known hypersensitivity to AZD4512 or any of the excipients of the product.
• Unresolved non-hematological AEs ≥ Grade 2 NCI CTCAE V5.0 from prior anticancer therapy, except for: (a) Alopecia, Fatigue, Grade 2 Peripheral neuropathy (peripheral neuropathy ≥ Grade 3 will be excluded), Endocrine disorders that are controlled with replacement therapy, or Stable vitiligo.
  • 3.Any severe and uncontrolled medical condition (eg, diabetes mellitus, any history of seizure, bleeding diathesis, hepatic failure, clinically significant liver disease including cirrhosis or hepatitis, unstable respiratory or cardiac conditions, active infection [bacterial, viral, fungal, or other infection]), any major infection that required hospitalization or treatment with IV or oral antimicrobials within 14 days of Day 1.
  • 4.Other malignancy within 2 years prior to screening with the exception of: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and considered to be at low risk of recurrence by the treating physician. b) Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer. c) Adequately treated carcinoma in situ without evidence of disease.
  • 5.History of non-infectious ILD/pneumonitis that has required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • 6.Serological status reflecting active HBV or HCV infections
  • 7.Active HIV infection. HIV-infected participants on effective anti-retroviral therapy with sustained undetectable viral load for longer than 6 months prior to enrollment are eligible for this study after confirmation from the sponsor.
  • 8.Cardiovascular disorder
• Participant has any medical or psychiatric condition which, in the opinion of the investigator or medical monitor, places the participant at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of participant safety or study results. Examples include major psychiatric illness and drug or alcohol abuse.

Lab values

• 10.Prior/Concomitant Therapy - Received adoptive cellular therapy such as autologous or donor Natural Killer (NK) cell or T-lymphocyte infusions [eg CAR-T cells]), or T-cell engager therapy, within 90 days prior to the first dose of study treatment. - Received any investigational drug chemotherapy, immunotherapy, immunosuppressant medication within 21 days (or 5 half-lives, whichever is shorter), or medications or herbal supplements known to be strong inhibitors of CYP3A within 14 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment. - Received radiation therapy with curative intent within 14 days prior to the first dose of study treatment. Localized palliative radiotherapy is permitted. - Received prior allogeneic HSCT, unless the transplant occurred > 180 days prior to the first scheduled dose and the participant has no active graft-versus-host disease requiring treatment and has been stable off immunosuppression for at least 2 months or received prior autologous HSCT unless the transplant occurred > 90 days prior to the first dose of study treatment and transplant-related toxicities are resolved to at least a Grade 1. - Received major surgery within 28 days prior to the first dose of study treatment. - Any concomitant medications known to prolong QTc and/or have a known risk for Torsades de Pointes within 5 half-lives prior to the first dose of AZD4512.

Other

• For women-only – currently pregnant (confirmed with positive pregnancy test) or breast-feeding (including when breast-feeding is interrupted) or intend to become pregnant during the study period.

• Age. Participants must be 18 years of age or older
• Measurable disease: FDG-PET-avid lymphomas: Must have at least one measurable FDG-PET-avid lesion, based on bi-dimensional assessment on PET and CT/MRI scan, defined as at least one nodal lesion > 1.5 cm in the long axis or at least one extra-nodal lesion > 1 cm in the long axis. FDG non-avid lymphomas: Must have at least one measurable based on bi-dimensional assessment on CT/MRI scan, defined as at least one nodal lesion > 1.5 cm in the long axis or at least one extra-nodal lesion > 1 cm in the long axis.
• ECOG Performance Status of ≤ 2.
• Life expectancy ≥ 12 weeks.
  • 5.Adequate organ and Bone Marrow function
• Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent and able to participate in all required study visits, evaluations, treatment plan, and other study procedures.